Summary of Work: The E. coli SOS system is an inducible system comprising some 20+ genes that are normally repressed but become induced when ongoing DNA replication is blocked by DNA lesions. It can also be expressed constitutively by genetic means in strains carrying a constitutively activated RecA protein. Part of the response is an error-prone activity that leads to greatly enhanced mutagenesis on both damaged (translesion synthesis) and undamaged DNA. Genetic experiments have revealed that this error-prone activity requires the action of the SOS-inducible UmuC, UmuD' and RecA proteins as well as DNA polymerase III. The umuD?2C complex has recently been identified as a DNA polymerase activity (pol V). The precise nature of the mutagenic events, including the pol III /pol V interplay, is still unknown. We have performed genetic experiments on the SOS mutator activity produced by the constitutively activated recA730 mutation in the absence of exogenously provoked DNA damage. These experiments suggest that the SOS mutator activity does not enhance the intrinsic error rate of replication. Instead, it amplifies pol III-generated normal polymerase errors through promotion of extension from the mispaired 3' termini, presumably by the action of pol V. We propose that a similar mechanism operates when the polymerase encounters DNA lesions. We have also discovered that the SOS mutator activity does not operate equally in both strands of the DNA replication fork. We estimate that the SOS mutator is at least an order of magnitude more efficient in the lagging strand. This hypothesis is consistent with the known enzymology of the lagging strand and the properties of the RecA nucleofilament.